【作者】 徐晓萍；

【导师】 张正春；

【作者基本信息】 苏州大学 ， 神经病学， 2006， 硕士

【摘要】 目的:通过大鼠局灶性脑缺血再灌注模型,研究曲美他嗪(TMZ)对脑缺血再灌注损伤的保护作用。方法:参照Zea Longa线栓法并加以改进建立局灶性脑缺血再灌注模型。健康雄性SD大鼠,随机分为假手术组(sham,NS 5ml/kg)、缺血再灌注组(I/R, NS 5ml/kg)、TMZ低剂量组(5mg/kg)、TMZ高剂量组(10mg/kg)。每日上午灌胃给药1次,连续用药2周,末次给药1h后施行手术。缺血2h后将线拔出再灌注。各组动物于再灌注24h后,进行大鼠神经功能缺损评分,评分后处死,行脑病理组织学观察、脑组织含水量及脑梗死体积检测,SOD、ATP酶活性和MDA含量测定。结果:1.大鼠缺血2h再灌注24h后,各组动物均出现神经缺损症状,缺血再灌注组尤为显著,TMZ组症状改善,大鼠神经功能损害评分降低(P<0.05);TMZ两个剂量组均使脑梗死体积缩小,脑含水量明显低于缺血再灌注组(P<0.01);病理组织学观察缺血再灌注组可见广泛的脑水肿,神经细胞固缩坏死,TMZ组病变减轻。2.大鼠缺血2h再灌注24h后,SOD、ATP酶活性明显降低,MDA含量显著增加,TMZ组SOD、ATP酶活性亦下降,MDA含量增加,但幅度较小,与缺血再灌注组相比有显著性差异(P<0.01)。结论:1.线栓法大鼠局灶性脑缺血再灌注损伤模型制作方法简单,病理改变与人脑缺血后的病变相似,具有较高的可靠性、重复性和实用性,是研究脑缺血再灌注损伤的较为理想的动物模型。2. TMZ能降低缺血再灌注后脑组织的MDA含量,增强SOD、ATP酶活力,可减轻脑缺血再灌注损伤,对脑细胞有明显的保护作用。更多还原

【Abstract】 Objective: In this study, the rat model of focal cerebral ischemia reperfusion was established with the middle cerebral artery occlusion by reversible inserting a nylon thread method ,to study the anti-cerebral ischemia reperfusion injury effects of TMZ and its mechanisms.Methods: The model of local ischemia-reperfusion in rats was established with the suture occluded method invented by Zea Longa and improved properly in our lab. Male SD rats were randomly divided into four groups: rats in group1 (sham)only received anesthesia and vessel separation; rats in group 2 received ischemia reperfusion operation and NS ig; in group 3 and 4 received ischemia-reperfusion and TMZ 5 mg/kg and 10mg/kg daily respectively. Rats in each group had been administered drugs for 2 weeks and then operation was done. Two hours later, we drew out the suture to recover perfusion. The neurological deficit score of rats in each group was evaluated after 24h ischemia-reperfusion. Then the subjects were killed .The infarct volume and water content were measured and pathological examination was performed. Influence of TMZ on activity of SOD, ATPase and the content of MDA in cerebral cortex were tested by spectrophotometry.Results: 1.All animals in each group manifested neuronal function disorder after 24h reperfusion following 2h ischemia. The symptom of model rats were especially marked. It was found that TMZ could improve the symptom of neurological deficit after cerebral ischemia reperfusion ,and decrease significantly the infarct volume and water content of cerebrum. There were great difference comparaed with the model group(P<0.05). Pathological findings showed that there were wide-ranging cerebral edema and neuronal cells necrosis. The finding also showed that TMZ treatment groups were able to abate pathological changes. 2. The activity of SOD and ATPase was remarkably lower and the content of MDA was higher in ischemia reperfusion group更多还原